Mechanisms of Blood Flow Restriction Exercise in Skeletal Muscle Adaptations

The maintenance of skeletal muscle mass is crucial for human health and long term survival. However, the aging process is associated with an involuntary loss of muscle mass and the inability to maximally stimulate muscle growth ultimately leading to sarcopenia. Extensive research has been conducted to determine the precise mechanisms by which nutrients, hormones and exercise regulate cell signaling events that convert the anabolic stimulus to a response that enhances cell size. Unfortunately, the research is incomplete considering the insufficient explanation for the impaired muscle synthetic response associated with aging. Interestingly, a novel style of exercise utilizing low-intensity resistance coupled with local vascular occlusion called “blood flow restriction” (BFR) exercise has emerged as an exercise that stimulates muscle growth and muscle protein synthesis to a similar extent for all adults. Research in the past two decades on BFR exercise has been primarily descriptive whereas a mechanistic explanation is lacking as to how a low intensity resistance stimulus is sufficient to promote an increase vi in muscle mass. Research in this dissertation is focused on investigating potential mechanisms that stimulate a muscle anabolic response following BFR exercise. Immediately following BFR exercise as the restriction cuffs are removed, reactive hyperemia occurs, and the increase in nutritive delivery to the muscle is believed to be one of the driving factors that stimulate muscle protein synthesis. Although, mimicking the effect of reactive hyperemia using a pharmacological vasodilator after low-intensity resistance exercise was insufficient to reproduce a similar increase in muscle protein synthesis or anabolic cell signaling. Moreover, mTORC1 is thought to be necessary and required for all cell growth signals; however, this mechanism has yet to be tested with BFR exercise. Use of the competitive mTORC1 inhibitor, rapamycin, determined that BFR exercise does in fact stimulate muscle protein synthesis through the activation of mTORC1. Lastly, metabolic stress such as the accumulation of lactate and G6P have been shown to play a role in the activation of mTORC1 in all muscle fibers contrary to high-intensity exercise that only stimulates fast twitch muscle fibers. Collectively, these studies further our understanding of the underlying mechanisms of BFR exercise.